Using the fruitfly, Drosophila melanogaster, as a model system, we have devised a screen for identifying genes that restrict cell proliferation in vivo. We take advantage of the technique of mitototic recombination to generate clones of mutant cells in the developing eye. By comparing their relative sizes, we can screen for mutations that lead to increased cell proliferation. Such mutations would disrupt the functions of genes that normally restrict cell proliferation. The goal of this project is to identify a number of such genes and molecularly characterize two of them. Two complementation groups has been identified by now in a primary screen of chromosome arm 2L: net (known gene, encode bHLH transcription factor) and nerpl (complement all known mutants from the region). Preliminary analysis of these mutants confirm their potential importance in controlling cell proliferation. Because basic mechanisms that regulate cell cycle progression are highly conserved between diverse species, e.g. Drosophila and humans, we anticipate that the genes identified in our screen will have human homologues and that the mechanisms that we define in Drosophila will also function in mammalian cells.